Our initial characterization of Dengue-infection-related immune repertoire has been ofthe B cell repertoires following different modes of infection-based pathology. This work combines a collaborative component (cells and patient information from Eva Harris, Poornima Parameswaran, and their colleagues), experimental manipulations to amplify receptor populations, and computational analysis of amplified sequences from high throughput immunome analysis. The past four months has provided our first detailed look at receptor repertoires in Dengue infection, and to my knowledge the first such analysis anywhere, yielding a number of rather striking observations that suggest both biological hypotheses and experimental followup. Although preliminary, these give a strong indication ofthe value of applying immunome analysis to infectious systems, (i) We observe, as with the original small scale sequencing set carried out in 2010, a strong clonal response in a subset of individuals with pathogenic conditions related to Dengue. (ii)We observe a reproducible appearance of small clones of cells who's appearance coincides with an infectious event but which persist for at least six months after exposure, (iii) We observe different patterns of appearance and maturation in Dengue 2 and Dengue 3 cohorts, suggesting potential mechanisms for the serotype-specific properties of these infectious agents in their effects (short and long-term) on the host. Followup work in this area will provide us the opportunity to determine the generality and significance of these observations and to addresses a series of specific questions related to understanding and management of infection: (i) Will receptor profiling be a valuable adjunct in identifying Dengue-related syndromes and predicting cases that will be severe? (ii) Will receptor profiles of Dengue cases provide specific candidates for immune receptor molecules that mediate unhealthy immune effects during secondary infection? (iii) Will the molecular signatures obtained from this analysis (combined with the extensive analysis in a number of other groups of additional molecular and immunological markers) be a useful clinical tool in guiding

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Specialized Center--Cooperative Agreements (U54)
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Special Emphasis Panel (ZAI1-DDS-M)
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University of California Irvine
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Hertz, Tomer; Beatty, P Robert; MacMillen, Zachary et al. (2017) Antibody Epitopes Identified in Critical Regions of Dengue Virus Nonstructural 1 Protein in Mouse Vaccination and Natural Human Infections. J Immunol 198:4025-4035
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